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Questions and Answers
What is the worldwide prevalence of Alkaptonuria?
What is the worldwide prevalence of Alkaptonuria?
- 1 case in 1 000 000 births
- 1 case in 250 000 births (correct)
- 1 case in 500 000 births
- 1 case in 100 000 births
In which country is the prevalence of Alkaptonuria the highest?
In which country is the prevalence of Alkaptonuria the highest?
- India
- Slovakia (correct)
- The Dominican Republic
- Jordan
How is the diagnosis of Alkaptonuria confirmed or excluded?
How is the diagnosis of Alkaptonuria confirmed or excluded?
- Blood test for phenylalanine and tyrosine levels
- Physical examination for symptoms
- Urine test for homogentisic acid using HPLC (correct)
- Genetic testing for AKU mutations
What is the effect of nitisinone on Alkaptonuria treatment?
What is the effect of nitisinone on Alkaptonuria treatment?
What is the effect of ascorbic acid on homogentisic acid excretion?
What is the effect of ascorbic acid on homogentisic acid excretion?
What is the approximate number of identified AKU sufferers in 40 countries?
What is the approximate number of identified AKU sufferers in 40 countries?
What is the recommended dietary restriction for Alkaptonuria treatment?
What is the recommended dietary restriction for Alkaptonuria treatment?
What is the name of the enzyme inhibited by nitisinone?
What is the name of the enzyme inhibited by nitisinone?
What causes the pigment to appear more rapidly in urine samples?
What causes the pigment to appear more rapidly in urine samples?
What is the primary cause of Alkaptonuria?
What is the primary cause of Alkaptonuria?
What is a common symptom of alkaptonuria in children and young adults?
What is a common symptom of alkaptonuria in children and young adults?
Where is homogentisic acid oxidase primarily found in mammalian systems?
Where is homogentisic acid oxidase primarily found in mammalian systems?
What is the term for the widespread deposition of pigment in alkaptonuria?
What is the term for the widespread deposition of pigment in alkaptonuria?
What is the ultimate product of the catabolism of homogentisic acid?
What is the ultimate product of the catabolism of homogentisic acid?
What is a common location for pigment deposition in alkaptonuria?
What is a common location for pigment deposition in alkaptonuria?
How is Alkaptonuria inherited?
How is Alkaptonuria inherited?
At what age do patients with alkaptonuria typically develop visible pigmentation?
At what age do patients with alkaptonuria typically develop visible pigmentation?
What is the prevalence of Alkaptonuria?
What is the prevalence of Alkaptonuria?
What is a common joint affected by alkaptonuria?
What is a common joint affected by alkaptonuria?
What is a possible complication of alkaptonuria?
What is a possible complication of alkaptonuria?
What happens to urine from patients with Alkaptonuria when exposed to air?
What happens to urine from patients with Alkaptonuria when exposed to air?
What is a possible outcome for older patients with alkaptonuria?
What is a possible outcome for older patients with alkaptonuria?
What is the name of the pigment formed from the accumulation of homogentisic acid and its oxidized derivative?
What is the name of the pigment formed from the accumulation of homogentisic acid and its oxidized derivative?
When do patients with Alkaptonuria usually excrete dark urine?
When do patients with Alkaptonuria usually excrete dark urine?
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Study Notes
Alkaptonuria (AKU)
- Caused by a deficiency of homogentisic acid oxidase, leading to the accumulation of homogentisic acid (HGA)
- HGA oxidase is found only in the liver and kidney, and plays a crucial role in the catabolism of phenylalanine and tyrosine
Etiology and Pathophysiology
- Inherited as an autosomal recessive trait, with consanguinity noted by Garrod
- A rare disorder affecting about 1 in 250,000 live births
- Deficiency of homogentisate dioxygenase leads to the accumulation of HGA and its oxidized derivative, benzoquinone acetic acid
- This can be polymerized to form a dark pigment, deposited in connective tissue
Clinical Abnormalities
- Urine from AKU patients darkens when exposed to air, especially if alkalinized
- Patients usually excrete acid urine of normal color, which turns dark on standing
- Infants may be recognized due to their cloth diapers turning black or brown when washed with alkaline soap or detergent
- Patients develop visible pigmentation (ochronosis) of the sclerae or cartilage of the ears after 30 years of age
- Pigment may also be seen in the corneal, buccal mucosa, nails, and skin
- Patients develop pain in weight-bearing joints, especially after 30 years of age
- Joint-replacement surgery may be necessary at a relatively young age
- Patients may become bedridden due to severe limitation of movement
Epidemiology
- Worldwide prevalence of AKU is 1 case in 250,000 births
- As of now, 950 AKU sufferers have been identified in 40 countries
- More prevalent in Slovakia, the Dominican Republic, India, and Jordan
- Highest prevalence is in Slovakia, where up to 1 in 19,000 are affected
Investigation and Diagnosis
- Diagnosis can be confirmed or excluded by collecting urine for 24 hours and determining the amount of HGA using HPLC or specific enzymatic methods
Treatment and Outcomes
- Recommended treatments include large doses of ascorbic acid (vitamin C) or dietary restriction of amino acids phenylalanine and tyrosine
- Nitisinone may be effective in treating AKU, by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase and blocking the production of HGA
- Low-dose nitisinone (2 mg/day) has been shown to reduce plasma and urine HGA by 95%
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